Regulation of T cell autoreactivity to MHC class II by controlling CD80 (B7-1) expression on B cells

International Immunology
A HasegawaT Tada

Abstract

Regulatory mechanisms of T cell autoreactivity to MHC class II molecules were studied in transgenic (Tg) mice with auto-I-Ak-reactive TCR alphabeta transgenes (designated as MS Tg mice). Our previous study revealed that the T cell tolerance established in autoreactive MS Tg mice was not due to either clonal deletion in the thymus, anergy or an active suppression in the periphery. We proposed a novel form of self tolerance termed 'clonal insufficiency', where autoreactive T cells were conditionally rendered unresponsiveness to self antigen in vivo, although retaining full potential reactivity in in vitro conditions. Here, we investigated the role of co-stimulatory molecules for the induction of self tolerance with 'clonal insufficiency'. MS Tg mice were mated with CD80 (B7-1) Tg mice in which B cells exclusively and constitutively expressed CD80 molecules. Both MS Tg mice and CD80 Tg mice by themselves showed no evidence for activation of T cells and B cells, whereas MS x CD80 double-Tg mice with a H-2k background revealed an abnormal increase in the number of splenocytes and in the expression of activation markers (CD69 and CD25) on CD4 T cells in the spleen. These results indicated that the self tolerance established in MS Tg ...Continue Reading

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